Oxidative stress with tau hyperphosphorylation in memory impaired 1,2-diacetylbenzene-treated mice

- 1,2-DAB produces ROS in hippocampal homogenates.
- 1,2-DAB hyperphosphorylates tau via GSK-3β.
- NAC, antioxidant, and GSK-3β inhibitor reduced tau phosphorylation.
- 1,2-DAB produces learning and memory impairment in mice.
- Memory impairment by 1,2-DAB might be related to ROS/GSK-3β/tau hyperphosphorylation.

Long-term exposure to organic solvent may be related to the incidence of neuronal diseases, such as, Alzheimer's disease, depression, multiple sclerosis, dementia, Parkinson's disease. Previously, the authors reported 1,2-diacetylbenzene (DAB; a neurotoxic metabolite of 1,2-diethylbenzene) causes central and peripheral neuropathies that lead to motor neuronal deficits. Furthermore, it is known DAB increases oxidative stress and protein adduct levels and impairs hippocampal neurogenesis in mice. The authors examined the relevance of oxidative stress and tau hyperphosphorylation in the hippocampus. Five-week-old male C57BL/6 mice were treated with 1 or 5 mg/kg/day DAB for 2 weeks. Neither overall body weight increases nor behavioral differences were observed after treatment, but kidney and liver weights decreased. Increased ROS production, activated glycogen synthase kinase-3β (GSK-3β) and tau hyperphosphorylation were observed in hippocampal homogenates. To assess memory impairment, the Morris Water Maze was used. Animals in the DAB-treated groups took longer to reach the platform. Movement patterns of DAB treated mice were more complicated and their swimming speeds were lower than those of controls. When SHSY5Y neuroblastoma cells were pretreated with NAC (an antioxidant) or a GSK-3β inhibitor, the expression of active GSK-3β and tau hyperphosphorylation were reduced. These results suggest ROS produced by DAB causes tau hyperphosphorylation via GSK-3β phosphorylation and it might be related to impaired memory deficit.